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THE THERAPEUTIC ANGIOGENESIS AND SYSTEMIC ENDOTHELIAL TONE
A166.E1557 JACC Maarch 9, 2010 Volume 55, issue 10A
VASCULAR DISEASE THE THERAPEUTIC ANGIOGENESIS AND SYSTEMIC ENDOTHELIAL TONE ACC Poster Contributions Georgia World Congress Center, Hall B5 Monday, March 15, 2010, 9:30 a.m.-10:30 a.m.
Session Title: Vascular Biology/Atherosclerosis/Basic Science Abstract Category: Vascular Biology/Atherosclerosis/Thrombosis/Endothelium Presentation Number: 1166-352 Authors: Gen Takagi, Masaaki Miyamoto, Ikuyo Takagi, Shuhei Tara, Yasuhiko Tabata, Kyoichi Mizuno, Nippon Medical School, Tokyo, Japan Background: Therapeutic angiogeneisis is a clinically effective strategy for patients with peripheral artery disease (PAD). Autologous bone marrow mononuclear cell is commonly used cell source in Japan. However it is still unknown whether local therapeutic angiogenesis could improve systemic vascular function after treatment. Also the mechanism is complicated because aoutologous bone marrow mononuclear cells secrete variable substances in response to ischemia. The purpose of this study was to determine whether single growth factor, basic fibroblast growth factor (b-FGF) administration improves systemic vascular function in patients with PAD. Methods: Limb ischemia was confirmed by digital subtraction angiography. After screening for preexisting coronary artery disease, cerebrovascular disease and malignancy, PAD patients suffering Fontaine class 3 or 4 were enrolled (n = 12, 56 ± 17 y/o). Gelatin hydrogel containing 600 μg of b-FGF, which is control release formula of b-FGF, was administered into the ischemic limbs. Transcutaneous oxygen tension (TcPO2) was examined to evaluate skin perfusion. Also, 99mTc-tetrofosmin scintigraphy was performed to examine tissue blood flow. Non-invasive endothelial function was determined by brachial artery endothelial-dependent flow - mediated dilatation (FMD) and endothelial-independent glyceryl trinitrate (GTN) mediated dilatation before and 4 weeks after treatment. Results: b-FGF administration improved visual analog pain scale (72.9 ± 26 to 6.8 ± 12, P < 0.01) and TcPO2 (14.7 ± 14 to 47.3 ± 16 mmHg, P < 0.01) at ischemic limbs 4 weeks after treatment. 99mTc-tetrofosmin scintigraphy score from opposite side (non-treated limbs) tend to be improved (0.64 ± 0.3 to 0.75 ± 0.3, P = 0.37), however it was not reached to the statistical significance. Compared to this, FMD was significantly improved (3.94 ± 1.4 to 7.83 ± 2.8 %, P < 0.01) at 4 weeks after the treatment. Endothelial-independent GTN mediated dilatation was not altered (8.8 ± 3.8 to 10.2 ± 4.9 %, NS). Conclusions: These findings suggest that local therapeutic angiogenesis, which induced by slow-released b-FGF, may restore systemic endothelium-dependent vasodilation in patients with PAD.
VASCULAR DISEASE THE THERAPEUTIC ANGIOGENESIS AND SYSTEMIC ENDOTHELIAL TONE ACC Poster Contributions Georgia World Congress Center, Hall B5 Monday, March 15, 2010, 9:30 a.m.-10:30 a.m.
Session Title: Vascular Biology/Atherosclerosis/Basic Science Abstract Category: Vascular Biology/Atherosclerosis/Thrombosis/Endothelium Presentation Number: 1166-352 Authors: Gen Takagi, Masaaki Miyamoto, Ikuyo Takagi, Shuhei Tara, Yasuhiko Tabata, Kyoichi Mizuno, Nippon Medical School, Tokyo, Japan Background: Therapeutic angiogeneisis is a clinically effective strategy for patients with peripheral artery disease (PAD). Autologous bone marrow mononuclear cell is commonly used cell source in Japan. However it is still unknown whether local therapeutic angiogenesis could improve systemic vascular function after treatment. Also the mechanism is complicated because aoutologous bone marrow mononuclear cells secrete variable substances in response to ischemia. The purpose of this study was to determine whether single growth factor, basic fibroblast growth factor (b-FGF) administration improves systemic vascular function in patients with PAD. Methods: Limb ischemia was confirmed by digital subtraction angiography. After screening for preexisting coronary artery disease, cerebrovascular disease and malignancy, PAD patients suffering Fontaine class 3 or 4 were enrolled (n = 12, 56 ± 17 y/o). Gelatin hydrogel containing 600 μg of b-FGF, which is control release formula of b-FGF, was administered into the ischemic limbs. Transcutaneous oxygen tension (TcPO2) was examined to evaluate skin perfusion. Also, 99mTc-tetrofosmin scintigraphy was performed to examine tissue blood flow. Non-invasive endothelial function was determined by brachial artery endothelial-dependent flow - mediated dilatation (FMD) and endothelial-independent glyceryl trinitrate (GTN) mediated dilatation before and 4 weeks after treatment. Results: b-FGF administration improved visual analog pain scale (72.9 ± 26 to 6.8 ± 12, P < 0.01) and TcPO2 (14.7 ± 14 to 47.3 ± 16 mmHg, P < 0.01) at ischemic limbs 4 weeks after treatment. 99mTc-tetrofosmin scintigraphy score from opposite side (non-treated limbs) tend to be improved (0.64 ± 0.3 to 0.75 ± 0.3, P = 0.37), however it was not reached to the statistical significance. Compared to this, FMD was significantly improved (3.94 ± 1.4 to 7.83 ± 2.8 %, P < 0.01) at 4 weeks after the treatment. Endothelial-independent GTN mediated dilatation was not altered (8.8 ± 3.8 to 10.2 ± 4.9 %, NS). Conclusions: These findings suggest that local therapeutic angiogenesis, which induced by slow-released b-FGF, may restore systemic endothelium-dependent vasodilation in patients with PAD.